Bansal R, Kumar M, Murray K, Pfeiffer S E
Department of Microbiology, University of Connecticut School of Medicine, Farmington 06030, USA.
Mol Cell Neurosci. 1996 Apr;7(4):276-88. doi: 10.1006/mcne.1996.0021.
Differentiating cells undergo developmentally regulated changes in cell-cell and cell-matrix adhesion that control migration through microenvironments, proliferation, and differentiation. The diversity of the patterns of expression of heparan sulfate proteoglycans (HSPGs), coupled with their interactions with extracellular matrix, cell adhesion molecules, and growth factors, has emphasized their critical importance in the regulation of these events. Syndecans (1-4), glypican, and cerebroglycan are membrane-associated HSPGs that have been implicated in these events in various tissues and several tumor cell lines. We have examined the developmental expression and FGF-2-mediated regulation of these HSPGs during differentiation within a specific lineage of primary cells, oligodendrocytes (OL). Northern analyses of highly purified, developmentally synchronized populations of OL-lineage cells at three stages of differentiation (early and late progenitors and mature OLs) showed that the expression of individual forms of these syndecans and glypican are developmentally regulated. Specifically, the level of expression of syndecan-2 and -4 and glypican mRNAs increased as the cells differentiated from proliferative late progenitors to postmitotic mature cells. The expression of syndecan-1 and -3 had the inverse developmental pattern. Therefore, these two sets of molecules may have different roles in regulating the onset of terminal differentiation in OLs. The levels of mRNA expression were regulated by FGF-2: in late progenitors, FGF-2 induced a doubling of the mRNA levels of syndecan-2, -3, and -4, while those for syndecan-1 and glypican remained unaffected; in mature OLs, the levels of syndecan-1 mRNA were up-regulated, the levels of syndecan-2 and -4 and glypican were down-regulated. These results suggest that the individual syndecan molecules have distinct functions during the differentiation process and that multiple levels of regulation must exist, leading to a changing repertoire of these molecules during OL lineage progression and myelinogenesis.
分化细胞在细胞间和细胞与基质的黏附中经历发育调控的变化，这些变化控制着细胞通过微环境的迁移、增殖和分化。硫酸乙酰肝素蛋白聚糖（HSPG）表达模式的多样性，以及它们与细胞外基质、细胞黏附分子和生长因子的相互作用，突显了它们在调控这些事件中的关键重要性。Syndecans（1 - 4）、磷脂酰肌醇蛋白聚糖和脑硫酸酯蛋白聚糖是与膜相关的HSPG，在各种组织和几种肿瘤细胞系的这些事件中发挥作用。我们研究了在原代细胞少突胶质细胞（OL）的特定谱系分化过程中这些HSPG的发育表达以及FGF - 2介导的调控。对处于分化三个阶段（早期和晚期祖细胞以及成熟OL）的高度纯化、发育同步的OL谱系细胞群体进行的Northern分析表明，这些syndecans和磷脂酰肌醇蛋白聚糖的各个形式的表达受发育调控。具体而言，随着细胞从增殖性晚期祖细胞分化为有丝分裂后成熟细胞，syndecan - 2和 - 4以及磷脂酰肌醇蛋白聚糖mRNA的表达水平增加。Syndecan - 1和 - 3的表达呈现相反的发育模式。因此，这两组分子在调控OL终末分化起始中可能具有不同作用。mRNA表达水平受FGF - 2调控：在晚期祖细胞中，FGF - 2使syndecan - 2、 - 3和 - 4的mRNA水平加倍，而syndecan - 1和磷脂酰肌醇蛋白聚糖的mRNA水平不受影响；在成熟OL中，syndecan - 1 mRNA水平上调，syndecan - 2和 - 4以及磷脂酰肌醇蛋白聚糖的水平下调。这些结果表明，各个syndecan分子在分化过程中具有不同功能，并且必须存在多个调控水平，导致这些分子在OL谱系进展和髓鞘形成过程中的组成不断变化。
